Zhang Yuying, Zhang Qianqian, Xin Wei, Liu Na, Zhang Hua
School of Biological Science and Technology, University of Jinan, Jinan, People's Republic of China.
Central Laboratory, Shandong Provincial Hospital, Shandong University, Jinan, People's Republic of China.
Drug Des Devel Ther. 2019 Jul 29;13:2591-2601. doi: 10.2147/DDDT.S180610. eCollection 2019.
Osteosarcoma is the most common malignancy of the bone in children and adolescents. There is an urgent need for the development of novel drugs to treat it. Nudol(1), a phenanthrene compound from the traditional Chinese medicine, , exhibited antiproliferative activity against osteosarcoma cells. Therefore, the aim of the present study was to investigate the role and underlying mechanism of nudol(1) as potential chemotherapy for osteosarcoma. Cell viability was determined by MTT assay. Cell-cycle phase distribution was analyzed by flow cytometry and Western blot. DAPI staining was used for morphology observation. Apoptosis was analysis via flow cytometry. The expression levels of mRNA and protein related to capase-mediated apoptotic pathway were detected by real-time PCR and western blotting. Migration was determined by wound healing assays. Nudol(1) significantly decreased cell viability in several cancer cell lines. Moreover, nudol(1) caused cell cycle arrest at G2/M phase in U2OS cells, and it also induced cell apoptosis through the caspase-dependent pathway. In addition, treatment with nudol(1) suppressed the migration of U2OS cells. The present study, for the first time, demonstrated effects of nudol(1) on OS in vitro and the potential molecular mechanisms. Accordingly, nudol(1) might have the potential for further development as a lead compound against bone tumor.
骨肉瘤是儿童和青少年中最常见的骨恶性肿瘤。迫切需要开发新型药物来治疗它。Nudol(1)是一种源自中药的菲类化合物，对骨肉瘤细胞具有抗增殖活性。因此，本研究的目的是探讨Nudol(1)作为骨肉瘤潜在化疗药物的作用及潜在机制。通过MTT法测定细胞活力。通过流式细胞术和蛋白质免疫印迹法分析细胞周期阶段分布。DAPI染色用于形态学观察。通过流式细胞术分析细胞凋亡。通过实时PCR和蛋白质免疫印迹法检测与半胱天冬酶介导的凋亡途径相关的mRNA和蛋白质表达水平。通过伤口愈合试验测定细胞迁移。Nudol(1)显著降低了几种癌细胞系的细胞活力。此外，Nudol(1)使U2OS细胞的细胞周期停滞在G2/M期，并且还通过半胱天冬酶依赖性途径诱导细胞凋亡。此外，用Nudol(1)处理可抑制U2OS细胞的迁移。本研究首次证明了Nudol(1)在体外对骨肉瘤的作用及潜在的分子机制。因此，Nudol(1)可能有潜力作为抗骨肿瘤的先导化合物进一步开发。
